scholarly journals Index60 Identifies Individuals at Appreciable Risk for Stage 3 Among an Autoantibody-Positive Population With Normal 2-Hour Glucose Levels: Implications for Current Staging Criteria of Type 1 Diabetes

2021 ◽  
Author(s):  
Brandon M. Nathan ◽  
Maria J. Redondo ◽  
Heba Ismail ◽  
Laura Jacobsen ◽  
Emily K. Sims ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Stage ◽  
Composite Measure ◽  
C Peptide ◽  
Glucose Levels ◽  
Younger Age ◽  
Design And Methods ◽  
Hla Dr3 ◽  
Positive Population

<u>Objective</u><b>:</b> We assessed whether Index60, a composite measure of fasting C-peptide, 60-minute C-peptide, and 60-minute glucose, could improve the metabolic staging of type 1 diabetes for progression to clinical disease (stage 3) among autoantibody positive (Ab+) individuals with normal 2-hour glucose values (<140 mg/dL). <p><u>Research Design and Methods</u>: We analyzed 3058 Type 1 Diabetes TrialNet Pathway to Prevention participants, with 2-hour glucose<140 mg/dL and Index60<1.00 values from baseline OGTTs. Characteristics associated with type 1 diabetes (younger age, greater autoantibody positivity [Ab+], higher HLA DR3-DQ2/DR4-DQ8 prevalence, lower C-peptide) were compared among four mutually exclusive groups: top 2-hour glucose quartile only [HI-2HGLU], top Index60 quartile only [HI-IND60], both top quartiles [HI-BOTH], neither top quartile [LO-BOTH]. Additionally, within the 2-hour glucose distribution of <140 mg/dL, and separately within the Index60<1.00 distribution, comparisons were made between those above or below the medians.</p> <p><u>Results</u>: HI-IND60 and HI-BOTH were younger, with greater frequency of >2 Ab+, and lower C-peptide levels than either HI-2HGLU or LO-BOTH (all p<0.001). The cumulative incidence for stage 3 was greater for HI-IND60 and HI-BOTH than either HI-2HGLU or LO-BOTH (all p<0.001). Those with Index60 values above the median were younger, had higher ≥2Ab+ (p<0.001) and DR3-DQ2/DR4-DQ8 prevalence (p<0.001), and lower AUC C-peptide levels (p<0.001) than those below. Those above the 2-hour glucose median had higher AUC C-peptide levels (p<0.001), but otherwise did not differ from those below. </p> <p><u>Conclusion</u>: Index60 identifies individuals with characteristics of type 1 diabetes at appreciable risk for progression who would otherwise be missed by 2-hour glucose staging criteria. </p>

scholarly journals Index60 Identifies Individuals at Appreciable Risk for Stage 3 Among an Autoantibody-Positive Population With Normal 2-Hour Glucose Levels: Implications for Current Staging Criteria of Type 1 Diabetes

2021 ◽  
Author(s):  
Brandon M. Nathan ◽  
Maria J. Redondo ◽  
Heba Ismail ◽  
Laura Jacobsen ◽  
Emily K. Sims ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Stage ◽  
Composite Measure ◽  
C Peptide ◽  
Glucose Levels ◽  
Younger Age ◽  
Design And Methods ◽  
Hla Dr3 ◽  
Positive Population

<u>Objective</u><b>:</b> We assessed whether Index60, a composite measure of fasting C-peptide, 60-minute C-peptide, and 60-minute glucose, could improve the metabolic staging of type 1 diabetes for progression to clinical disease (stage 3) among autoantibody positive (Ab+) individuals with normal 2-hour glucose values (<140 mg/dL). <p><u>Research Design and Methods</u>: We analyzed 3058 Type 1 Diabetes TrialNet Pathway to Prevention participants, with 2-hour glucose<140 mg/dL and Index60<1.00 values from baseline OGTTs. Characteristics associated with type 1 diabetes (younger age, greater autoantibody positivity [Ab+], higher HLA DR3-DQ2/DR4-DQ8 prevalence, lower C-peptide) were compared among four mutually exclusive groups: top 2-hour glucose quartile only [HI-2HGLU], top Index60 quartile only [HI-IND60], both top quartiles [HI-BOTH], neither top quartile [LO-BOTH]. Additionally, within the 2-hour glucose distribution of <140 mg/dL, and separately within the Index60<1.00 distribution, comparisons were made between those above or below the medians.</p> <p><u>Results</u>: HI-IND60 and HI-BOTH were younger, with greater frequency of >2 Ab+, and lower C-peptide levels than either HI-2HGLU or LO-BOTH (all p<0.001). The cumulative incidence for stage 3 was greater for HI-IND60 and HI-BOTH than either HI-2HGLU or LO-BOTH (all p<0.001). Those with Index60 values above the median were younger, had higher ≥2Ab+ (p<0.001) and DR3-DQ2/DR4-DQ8 prevalence (p<0.001), and lower AUC C-peptide levels (p<0.001) than those below. Those above the 2-hour glucose median had higher AUC C-peptide levels (p<0.001), but otherwise did not differ from those below. </p> <p><u>Conclusion</u>: Index60 identifies individuals with characteristics of type 1 diabetes at appreciable risk for progression who would otherwise be missed by 2-hour glucose staging criteria. </p>

scholarly journals Efficacy of GAD-alum immunotherapy associated with HLA-DR3-DQ2 in recently diagnosed type 1 diabetes

Diabetologia ◽  
2020 ◽  
Vol 63 (10) ◽  
pp. 2177-2181 ◽  
Author(s):  
Ulf Hannelius ◽  
Craig A. Beam ◽  
Johnny Ludvigsson
Keyword(s):  
Type 1 Diabetes ◽  
Treatment Effect ◽  
Repeated Measures ◽  
C Peptide ◽  
Recent Onset ◽  
Individual Level ◽  
Onset Type ◽  
Hla Dr3 ◽  
Effect Ratio

Abstract Aims/hypothesis The aim of this study was to determine if retention of C-peptide following immunotherapy using recombinant GAD65 conjugated to aluminium hydroxide (GAD-alum) is influenced by HLA risk haplotypes DR3-DQ2 and DR4-DQ8. Methods HLA-dependent treatment effect of GAD-alum therapy on C-peptide retention in individuals with recent-onset type 1 diabetes was evaluated using individual-level patient data from three placebo-controlled, randomised clinical trials using a mixed repeated measures model. Results A significant and dose-dependent effect was observed in individuals positive for the genotypes that include HLA-DR3-DQ2 but not HLA-DR4-DQ8 and in the broader subgroup of individuals positive for all genotypes that include HLA-DR3-DQ2 (i.e. including those also positive for HLA-DR4-DQ8). Higher doses (three or four injections) showed a treatment effect ratio of 1.596 (95% CI 1.132, 2.249; adjusted p = 0.0035) and 1.441 (95% CI 1.188, 1.749; adjusted p = 0.0007) vs placebo for the two respective HLA subgroups. Conclusions/interpretation GAD65-specific immunotherapy has a significant effect on C-peptide retention in individuals with recent-onset type 1 diabetes who have the DR3-DQ2 haplotype.

scholarly journals Measurement Of Peak C-Peptide At Diagnosis Informs Glycemic Control But Not Hypoglycemia In Adults With Type 1 Diabetes

2021 ◽  
Author(s):  
Alice L J Carr ◽  
Richard A Oram ◽  
Shannon M Marren ◽  
Timothy J McDonald ◽  
Parth Narendran ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Dose ◽  
Glucose Monitoring ◽  
Glycemic Variability ◽  
Newly Diagnosed ◽  
C Peptide ◽  
Glucose Levels ◽  
Normal Glucose ◽  
The Impact

Abstract Context High residual C-peptide in longer duration type 1 diabetes associates with fewer hypoglycemic events and reduced glycemic variability. Little is known about the impact of C-peptide close-to-diagnosis. Objective Using continuous glucose monitoring (CGM) data from a study of newly diagnosed adults with type 1 diabetes, we aimed to explore if variation in C-peptide close-to-diagnosis influenced glycemic variability and risk of hypoglycemia. Design We studied newly diagnosed adults with type 1 diabetes who wore a Dexcom G4 CGM for 7 days as part the EXTOD study. We examined the relationship between peak stimulated C-peptide and glycemic metrics of variability and hypoglycemia for 36 CGM traces from 23 participants. Results For every 100 pmol/l increase in peak C-peptide, percentage time spent range 3.9-10 mmol/l was increased by 2.4% [95% CI: 0.5,4.3], p=0.01) with a reduction in time spent in level 1 hyperglycemia (&gt; 10 mmol/l) and level 2 hyperglycemia (&gt; 13.9 mmol/l) by 2.6% [95% CI: -4.9, -0.4, p=0.02) and 1.3% [95% CI: -2.7, -0.006], p= 0.04) respectively. Glucose levels were on average lower by 0.19 mmol/l ([95 % CI: -0.4,0.02], p=0.06) and standard deviation reduced by 0.14 [95% CI: -0.3, -0.02], p=0.02). Hypoglycemia was not common in this group and no association was observed between time spent in hypoglycemia (p=0.97) or hypoglycemic risk (p=0.72). There was no association between peak C-peptide and insulin dose adjusted HbA1c (IDAA1c, p=0.45). Conclusions C-peptide associates with time spent in normal glucose range and with less hyperglycemia, but not risk of hypoglycemia in newly diagnosed people with type 1 diabetes.

scholarly journals Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial

2021 ◽  
Author(s):  
Johnny Ludvigsson ◽  
Zdenek Sumnik ◽  
Terezie Pelikanova ◽  
Lia Nattero Chavez ◽  
Elena Lundberg ◽  
...  
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Treatment Effect ◽  
Vitamin D Supplementation ◽  
Double Blind ◽  
C Peptide ◽  
Recent Onset ◽  
Hla Dr3 ◽  
Effect Ratio

<b>Objectives:</b> To evaluate the efficacy of intra-lymphatic GAD-alum therapy together with vitamin D supplementation on preserving endogenous insulin secretion in all patients with Type 1 diabetes (T1D) or in a genetically pre-specified subgroup. <p><b>Research Design and Methods:</b> In a multicenter, randomized, placebo-controlled double-blind trial (NCT03345004), 109 patients aged 12-24 (16.4 ± 4.1) years with a diabetes duration of 7-193 (88.8 ± 51.4) days, elevated serum GAD65 autoantibodies (GADA) and a fasting serum C-peptide >0.12 nmol/L, were recruited. Subjects were randomized to receive either three intra-lymphatic injections (one month apart) with 4 µg GAD-alum and oral vitamin D (2000 IE daily for 120 days), or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15-month.</p> <p><b>Results:</b> </p> <p>Primary endpoint was not met in the full analysis set (treatment effect ratio 1.091, CI 0.845-1.408, p = 0.5009). However, GAD-alum treated patients carrying HLA DR3-DQ2 (n=29, defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557, CI 1.126-2.153, p = 0.0078) after 15 months compared to placebo individuals with the same genotype (n=17). Several secondary end points showed supporting trends and a positive effect was seen in partial remission (IDAA1c≤9, p=0.0310). Minor transient injection site reactions were reported. </p> <p><b>Conclusions:</b> Intra-lymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent onset T1D carrying HLA DR3-DQ2. This constitutes a disease modifying treatment for T1D with a precision medicine approach.</p>

scholarly journals GAD65 antibody prevalence and association with c-peptide, HLA class II alleles in Beninese patients with type 1 diabetes

2017 ◽  
Vol 5 (8) ◽  
pp. 3406
Author(s):  
Kaossarath A. Fagbemi ◽  
Simon Azonbakin ◽  
Marius Adjagba ◽  
Razack Osseni ◽  
Rafiath Babio ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Sensitivity And Specificity ◽  
Class Ii ◽  
Hla Class Ii ◽  
Acid Decarboxylase ◽  
C Peptide ◽  
Significant Difference ◽  
Hla Dr3 ◽  
Hla Class Ii Alleles

Background: Antibodies to glutamic acid decarboxylase and particularly their isoforms in 65 kDa are one of markers for the diagnosis of the type 1 diabetes (T1D). The aim of this study is to assess the prevalence of GAD65 antibodies (GAD65Ab) and investigate the association of GAD65Ab with C-peptide values, HLA Class II alleles genotyping. The diagnosis of T1D was set up according to American Diabetes Association criteria.Methods: Radioimmunoassay was used to determine the GAD65Ab and C-peptide values. Class II HLA genotyping was performed in 51 patients with T1D and 51 healthy unrelated as control by using the PCR-SSP method. The sensitivity and specificity of the tests were calculated by standard formula.Results: Result revealed that GAD65Ab were present in 74.5% (38/51) of the patients with T1D. There was no significant difference between the positivity or the negativity of GAD65Ab and gender, onset and duration of diabetes, frequencies of HLA-DR4, HLA-DR3-DR4, HLA-DQB1*0201. However, GAD65Ab values are linked to C-peptide concentration (χ2 =15.73, P=0.0001), the presence of HLA-DR3 (χ2 =9.75, P= 0.002), HLA-DQA1*0501 (χ2 =4.09, P= 0.043) alleles. The GAD65Ab test sensitivity and specificity were 74.5% and 94.1%, respectively. The C-peptide test showed a sensitivity around 82.4 % and 86.3 % for the specificity.Conclusions: GAD65Ab showed to be a valuable early predictive marker and is associated with the risk to develop of T1D.

scholarly journals Islet autoantibody level distributions in type 1 diabetes and their association with genetic and clinical characteristics

2021 ◽  
Author(s):  
Sian Louise Grace ◽  
Jack Bowden ◽  
Helen C Walkey ◽  
Akaal Kaur ◽  
Shivani Misra ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Clinical Characteristics ◽  
Islet Autoantibody ◽  
Additional Information ◽  
Younger Age ◽  
Age Of Diagnosis ◽  
Hla Dr3 ◽  
Islet Antigen ◽  
Autoantibody Level

Positivity for islet autoantibodies is used for diagnosis of type 1 diabetes. However, the importance of the autoantibody level at diagnosis of type 1 diabetes is not clear. Here, we assessed the association of glutamate decarboxylase (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) autoantibody levels, measured using radiobinding assays, on genetic and clinical characteristics at diagnosis of 1536 participants with diabetes who were positive for these autoantibodies. We show that GADA and IA-2A levels had bimodal distributions, but ZnT8A level did not. The comparison of genetic and clinical characteristics between high and low level categories showed high GADA level was associated with older age at diagnosis, female sex and HLA-DR3-DQ2, whereas high IA-2A level was associated with younger age of diagnosis, ZnT8A positivity and HLA-DR4-DQ8. We replicated our findings in an independent cohort of 427 people with type 1 diabetes where autoantibodies were measured using enzyme-linked immunosorbent assays. In conclusion, Islet autoantibody levels provide additional information over positivity in type 1 diabetes at diagnosis. The bimodality of islet autoantibody levels highlights the novel aspect of heterogeneity of type 1 diabetes which may have implications on prediction, treatment and prognosis.

scholarly journals Sleep in Caregivers of Children With Type 1 Diabetes

2018 ◽  
Vol 45 (1) ◽  
pp. 80-86 ◽  
Author(s):  
Christine A. Feeley ◽  
Marilyn Clougherty ◽  
Linda Siminerio ◽  
Denise Charron-Prochownik ◽  
Anna L. Allende ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Poor Sleep ◽  
Demographic Information ◽  
Short Sleep Duration ◽  
White Children ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Nighttime Sleep ◽  
Design And Methods

Purpose The purpose of this study was to explore caregivers’ descriptions of their experience of nighttime sleep. Design and Methods Caregivers (N = 22) of children 10 to 18 years of age with type 1 diabetes (T1D) were recruited for this descriptive study. Anonymous questionnaires contained demographic information and both open- and closed-ended questions that focused on caregiving as it related to sleep. Open-ended questions were reviewed to help understand the effect of nocturnal caregiving activities on parental sleep. Results The sample of caregivers were all female and had a mean age of 43 years; 96% graduated high school, 68% were married or partnered, and 100% were white. Children had been diagnosed with T1D for a mean of 5 years, with a mean age of 12.2 years. Caregivers reported short sleep duration (mean, 5.8 hours). Over half of the participants reported they required ≥7 hours of sleep to feel their best, 64% indicated trouble sleeping at night, and 86% reported that caregiving interfered with their nighttime sleep, while 54% responded that sleep was “very important.” Content analysis of the open-ended questions revealed 2 themes: (1) anxiety about the child’s blood glucose levels and (2) nighttime disruptions. Conclusions Caregivers are frequently sleep deprived and worry about their child’s nighttime glucose. Caregiving duties, anxiety, and sleep fragmentation may contribute to their poor sleep.

scholarly journals Detection of C-peptide in human hair and nail: a comparison between healthy persons and persons with type 1 diabetes

2020 ◽  
Vol 8 (1) ◽  
pp. e001297
Author(s):  
Jamal M Salih ◽  
Darya S Abdulateef
Keyword(s):  
Type 1 Diabetes ◽  
Control Group ◽  
C Peptide ◽  
Hair Samples ◽  
Positive Correlations ◽  
Design And Methods ◽  
And Control ◽  
Control Study ◽  
Healthy Persons

ObjectivesSerum and urinary C-peptide has clinical implications in people with/without diabetes. Recently, C-peptide was detected in hair samples of healthy adults but not studied in people with diabetes. It is not known whether C-peptide can be detectable in nail tissue or not. This study aims to assess the detection of C-peptide in hair and nail samples and to find whether hair and nail C-peptide levels are different in type 1 diabetes mellitus (T1DM) compared with healthy individuals.Research design and methodsIn a prospective case-control study on 41 subjects with T1DM and 42 control subjects, hair and nail samples were collected and prepared. C-peptide was extracted by incubating the samples with methanol and measuring the extract with an immunoassay. The hair and nail C-peptide values were compared between the T1DM and control group and their correlations with each other and with other variables were assessed with a significant level set at 0.05.ResultsHair and nail C-peptide levels were detected in both groups, with significantly lower values in T1DM compared with the control group. T1DM with >7-year diabetes duration had significantly lower C-peptide in serum, nails and hair. Hair and nail C-peptide levels have significant positive correlations with each other and negative correlations with age.ConclusionsWe conclude that C-peptide are detectable in the hair and nails of healthy persons and persons with T1DM. Compared with the healthy persons, persons with T1DM had significantly lower hair and nail C-peptide and significant hair/nail C-peptide reduction after 7 years of diagnosis. Our results suggest that hair and nails are suitable matrices for the measurement of C-peptide in healthy persons and persons with T1DM.

scholarly journals Better HbA1c during the first years after diagnosis of type 1 diabetes is associated with residual C peptide 10 years later

2020 ◽  
Vol 8 (1) ◽  
pp. e000819
Author(s):  
Annika Grönberg ◽  
Daniel Espes ◽  
Per-Ola Carlsson
Keyword(s):  
Type 1 Diabetes ◽  
Children And Adolescents ◽  
Entire Study ◽  
C Peptide ◽  
Peptide Concentration ◽  
Grand Average ◽  
Predominantly Female ◽  
Design And Methods

ObjectiveTo identify the factors associated with residual C peptide production at least 10 years after diagnosis in children and adolescents with type 1 diabetes.Research design and methods73 children and adolescents (<25 years), born in 1988–2005, diagnosed with type 1 diabetes were included during the 4-year study period (2013–2016). At least 10 years after diagnosis, we measured any remaining C peptide concentration using an ultrasensitive C peptide ELISA (≥1.17 pmol/L). The average hemoglobin A1c (HbA1c) was calculated during each of the 10 years after diagnosis and further grand average was calculated for the entire study period.ResultsC peptide was detectable in 38% of participants. The C peptide concentration was 4.3±5.3 pmol/L. At onset of type 1 diabetes, participants were on average approximately 5 years of age, and their average HbA1c was 9.4% (79 mmol/mol). During the first 3 years after diagnosis, HbA1c was lower in the group with detectable C peptide at follow-up ≥10 years later. Moreover, detectable C peptide was more common among female participants. Body mass index SD scores had not increased since the 1-year follow-up, but were higher in patients with measurable C peptide. Nine participants (12%) had been diagnosed with celiac disease and two (3%) with hypothyreosis. Eighteen (25%) participants had retinopathy.ConclusionsChildren and adolescents with detectable C peptide after more than 10 years of diabetes duration were predominantly female and had better HbA1c than others during the first 3 years after diagnosis.

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